Genomic alterations in neuroendocrine prostate cancer: A systematic review and meta-analysis.

Background: Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. We performed a systematic review and meta-analysis to evaluate the prevalence of genomic alterations in NEPC and better understand its molecular features to potentially inform precision medicine.

Methods: EMBASE, PubMed, and Cochrane Central Register of Controlled Trials databases were searched for eligible studies until March 2022. Study qualities were assessed using the Q-genie tool. The prevalence of gene mutations and copy number alterations (CNAs) were extracted, and meta-analysis was performed using R Studio with package.

Results: A total of 14 studies with 449 NEPC patients were included in this meta-analysis. The most frequently mutated gene in NEPC was (49.8%), and the prevalence of deleterious mutations in was 16.8%. Common CNAs in NEPC included loss (58.3%), loss (42.8%), loss (37.0%), amplification (28.2%), and amplification (22.9%). alterations and concurrent and alterations were remarkably common in NEPC, with a prevalence of 83.8% and 43.9%, respectively. Comparative analyses indicated that the prevalence of (concurrent) alterations was significantly higher in de novo NEPC than in treatment-emergent NEPC (t-NEPC).

Conclusions: This study presents the comprehensive prevalence of common genomic alterations and potentially actionable targets in NEPC and reveals the genomic differences between de novo NEPC and t-NEPC. Our findings highlight the importance of genomic testing in patients for precision medicine and provide insights into future studies exploring different NEPC subtypes.